TRP Channel Cannabinoid Receptors in Skin Sensation, Homeostasis, and Inflammation.

“In the skin, cannabinoid lipids, whether of endogenous or exogenous origin, are capable of regulating numerous sensory, homeostatic and inflammatory events.

Although many of these effects are mediated by metabotropic CB receptors, a growing body of evidence has revealed that multiple members of the transient receptor potential (TRP) ion channel family can act as “ionotropic cannabinoid receptors”.

Furthermore, many of these same TRP channels are intimately involved in cutaneous processes that include the initiation of pain, temperature, and itch perception, the maintenance of epidermal homeostasis, the regulation of hair follicles and sebaceous glands, and the modulation of dermatitis.

Ionotropic cannabinoid receptors therefore represent potentially attractive targets for the therapeutic use of cannabinoids to treat sensory and dermatological diseases.

Furthermore, the interactions between neurons and other cell types that are mediated by cutaneous ionotropic cannabinoid receptors are likely to be recapitulated during physiological and pathophysiological processes in the central nervous system and elsewhere, making the skin an ideal setting in which to dissect general complexities of cannabinoid signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/24915599

Endocannabinoid system in cancer cachexia.

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“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

The endocannabinoid signaling system in cancer.

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“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

Anticancer activity of anandamide in human cutaneous melanoma cells.

“Cannabinoids are implicated in the control of cell proliferation, but little is known about the role of the endocannabinoid system in human malignant melanoma. This study was aimed at characterizing the in vitro antitumor activity of anandamide (AEA) in A375 melanoma cells…

 Overall, these findings demonstrate that AEA induces cytotoxicity against human melanoma cells in the micromolar range of concentrations through a complex mechanism, which involve COX-2 and LOX-derived product synthesis and CB1 activation. Lipid raft modulation, probably linked to GPR55 activation, might also have a role.”

http://www.ncbi.nlm.nih.gov/pubmed/24041928

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

“∆9 -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases.

Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors…

CONCLUSIONS:

Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors.

This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23889474

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.

“Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors.

Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation.

Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation.

OBJECTIVE:

We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors.

CONCLUSION:

The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process.

 Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.”

http://www.ncbi.nlm.nih.gov/pubmed/17157480

Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.

“A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.

CONCLUSIONS AND IMPLICATIONS:

These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23869687

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice.

“Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice…

The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/23837590

Cannabis Ingredient Can Help Cancer Patients Regain Their Appetites And Sense Of Taste

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“The active ingredient in cannabis can improve the appetites and sense of taste in cancer patients, according to a new study published online in the cancer journal, Annals of Oncology  today.

Loss of appetite is common among cancer patients, either because the cancer itself or its treatment affects the sense of taste and smell, leading to decreased enjoyment of food. This, in turn, can lead to weight loss, anorexia, a worse quality of life and decreased survival; therefore, finding effective ways of helping patients to maintain a good diet and consume enough calories is an important aspect of their treatment.

The majority of THC-treated patients (64%) had increased appetite, three patients (27%) showed no change, and one patient’s data was incomplete. No THC-treated patients showed a decrease in appetite. By contrast, the majority of patients receiving placebo had either decreased appetite (50%) or showed no change (20%).

Although there was no difference in the total number of calories consumed by both groups, the THC-treated patients tended to increase the proportion of protein that they ate, and 55% reported that savoury foods tasted better, whereas no patients in the placebo group reported an increased liking for these foods. (Cancer patients often find that meat smells and tastes unpleasant and, therefore, they eat less of it).

In addition, THC-treated patients reported better quality of sleep and relaxation than in the placebo group.”

More:  http://www.medicalnewstoday.com/articles/217062.php